Photospheric and chromospheric magnetic activity of seismic solar analogs. Observational inputs on the solar/stellar connection from Kepler and Hermes

We identify a set of 18 solar analogs among the seismic sample of solar-like stars observed by the Kepler satellite rotating between 10 and 40 days. This set is constructed using the asteroseismic stellar properties derived using either the global oscillation properties or the individual acoustic frequencies. We measure the magnetic activity properties of these stars using observations collected by the photometric Kepler satellite and by the ground-based, high-resolution Hermes spectrograph mounted on the Mercator telescope. The photospheric (Sph) and chromospheric (S index) magnetic activity levels of these seismic solar analogs are estimated and compared in relation to the solar activity. We show that the activity of the Sun is comparable to the activity of the seismic solar analogs, within the maximum-to-minimum temporal variations of the 11-year solar activity cycle 23. In agreement with previous studies, the youngest stars and fastest rotators in our sample are actually the most active. The activity of stars older than the Sun seems to not evolve much with age. Furthermore, the comparison of the photospheric, Sph, with the well-established chromospheric, S index, indicates that the Sph index can be used to provide a suitable magnetic activity proxy which can be easily estimated for a large number of stars from space photometric observations.Comment: Accepted for publication in A&

Mobilizing Greater Crop and Land Potentials with Conservation Agriculture

The engine that supplies food and agricultural products is the way we farm. The current dominant engine of conventional tillage farming based on the Green Revolution agriculture mind-set is faltering and needs to be replaced to meet the Sustainable Development Goals (SDGs) and the future food and agricultural demands by consumers and society. This chapter elaborates on the alternate no-till Conservation Agriculture (CA) paradigm (involving no-till seeding in soils with mulch cover and in diversified cropping systems). This new paradigm of CA is able to raise productivity sustainably and efficiently, reduce inputs, regenerate degraded land, minimize soil erosion, and harness the flow of ecosystem services. CA is an ecosystems approach to regenerative farming which is capable of enhancing the economic and environmental performance of crop production and land management that can contribute to achieving several SDGs. The new CA paradigm also promotes a mind-set change of producing ‘more from less’ inputs, the key attitude needed to move towards sustainable production based on agro-ecological intensification of output. CA is spreading globally in all continents at an annual rate of around 10 M ha of cropland. The current (in 2015/16) spread of CA is approximately 180 M ha, of which 48% is located in the Global South. CA not only provides the possibility of increased crop yields and profit for the low input smallholder farmer, it also provides a pro-poor rural and agricultural development model to support sustainable agricultural intensification in low income countries in an affordable manner for poverty alleviation, food security and economic development. However, for SDGs to contribute real lasting value to the quality of human life and to nature, the current and future human and ethical consequences of the uncontrolled consumer demands and pressures placed upon agricultural production by the food and agriculture system as a whole must be addressed

Time to embrace access programmes for medicines: Lessons from the South African flucytosine access programme.

BACKGROUND: Cryptococcal Meningitis (CM) is estimated to cause 181,000 deaths annually; with the majority occurring in Sub Saharan Africa. Flucytosine is recommended by the World Health Organization as part of the treatment for CM. Widespread use of flucytosine could reduce mortality in hospital by as much as 40% compared to the standard of care, yet due to market failure quality assured flucytosine remains unregistered and largely inaccessible throughout Africa. METHODS: The recently established South African flucytosine clinical access programme is an attempt to address market failure which led to a lack of public-sector access to flucytosine for cryptococcal meningitis, by making the medicine freely available to tertiary hospitals in South Africa. RESULTS: Between November 2018 and September 2019, 327 CM patients received flucytosine through this programme, with efforts to support sustainable national scale up presently ongoing. We describe why this programme was needed, its catalytic potential, what is still required to ensure widespread access to flucytosine, and observation from this experience that may have wider relevance. CONCLUSIONS: The South African Flucytosine Access Programme illustrates how access programmes may be one part of the solution to addressing the vicious cycle of perceived low demand, limiting manufacturer interest in specific product markets

Rituximab suppresses disease activity after natalizumab withdrawal: an exploratory study

Background Natalizumab is highly effective in reducing multiple sclerosis disease activity; however it carries a risk of progressive multifocal leukoencephalopathy, that represents the main reason of drug discontinuation. After natalizumab withdrawal, reactivation of disease is soon observed and, until now, it is not known which treatment strategy should be followed after natalizumab discontinuation. Aim of this study is to evaluate rituximab efficacy in controlling disease activity after natalizumab withdrawal

Switching Multiple Sclerosis Patients with Breakthrough Disease to Second-Line Therapy

BACKGROUND: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. METHODS: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. RESULTS: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p =  0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004). CONCLUSIONS: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies

A Novel Adeno-Associated Viral Variant for Efficient and Selective Intravitreal Transduction of Rat Müller Cells

BACKGROUND:The pathologies of numerous retinal degenerative diseases can be attributed to a multitude of genetic factors, and individualized treatment options for afflicted patients are limited and cost-inefficient. In light of the shared neurodegenerative phenotype among these disorders, a safe and broad-based neuroprotective approach would be desirable to overcome these obstacles. As a result, gene delivery of secretable-neuroprotective factors to Müller cells, a type of retinal glia that contacts all classes of retinal neurons, represents an ideal approach to mediate protection of the entire retina through a simple and innocuous intraocular, or intravitreal, injection of an efficient vehicle such as an adeno-associated viral vector (AAV). Although several naturally occurring AAV variants have been isolated with a variety of tropisms, or cellular specificities, these vectors inefficiently infect Müller cells via intravitreal injection. METHODOLOGY/PRINCIPAL FINDINGS:We have previously applied directed evolution to create several novel AAV variants capable of efficient infection of both rat and human astrocytes through iterative selection of a panel of highly diverse AAV libraries. Here, in vivo and in vitro characterization of these isolated variants identifies a previously unreported AAV variant ShH10, closely related to AAV serotype 6 (AAV6), capable of efficient, selective Müller cell infection through intravitreal injection. Importantly, this new variant shows significantly improved transduction relative to AAV2 (>60%) and AAV6. CONCLUSIONS/SIGNIFICANCE:Our findings demonstrate that AAV is a highly versatile vector capable of powerful shifts in tropism from minor sequence changes. This isolated variant represents a new therapeutic vector to treat retinal degenerative diseases through secretion of neuroprotective factors from Müller cells as well as provides new opportunities to study their biological functions in the retina

Targeting vaccinations for the licensed dengue vaccine: considerations for serosurvey design

Background The CYD-TDV vaccine was unusual in that the recommended target population for vaccination was originally defined not only by age, but also by transmission setting as defined by seroprevalence. WHO originally recommended countries consider vaccination against dengue with CYD-TDV vaccine in geographic settings only where prior infection with any dengue serotype, as measured by seroprevalence, was >170% in the target age group. Vaccine was not recommended in settings where seroprevalence was <50%. Test-and-vaccinate strategies suggested following new analysis by Sanofi will still require age-stratified seroprevalence surveys to optimise age-group targeting. Here we address considerations for serosurvey design in the context of vaccination program planning. Methods To explore how the design of seroprevalence surveys affects estimates of transmission intensity, 100 age-specific seroprevalence surveys were simulated using a beta-binomial distribution and a simple catalytic model for different combinations of age-range, survey size, transmission setting, and test sensitivity/specificity. We then used a Metropolis-Hastings Markov Chain Monte-Carlo algorithm to estimate the force of infection from each simulated dataset. Results Sampling from a wide age-range led to more accurate estimates than merely increasing sample size in a narrow age-range. This finding was consistent across all transmission settings. The optimum test sensitivity and specificity given an imperfect test differed by setting with high sensitivity being important in high transmission settings and high specificity important in low transmission settings. Conclusions When assessing vaccination suitability by seroprevalence surveys, countries should ensure an appropriate age-range is sampled, considering epidemiological evidence about the local burden of disease

The oxysterol 27-hydroxycholesterol increases β-amyloid and oxidative stress in retinal pigment epithelial cells

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) and age-related macular degeneration (AMD) share several pathological features including β-amyloid (Aβ) peptide accumulation, oxidative damage, and cell death. The causes of AD and AMD are not known but several studies suggest disturbances in cholesterol metabolism as a culprit of these diseases. We have recently shown that the cholesterol oxidation metabolite 27-hydroxycholesterol (27-OHC) causes AD-like pathology in human neuroblastoma SH-SY5Y cells and in organotypic hippocampal slices. However, the extent to which and the mechanisms by which 27-OHC may also cause pathological hallmarks related to AMD are ill-defined. In this study, the effects of 27-OHC on AMD-related pathology were determined in ARPE-19 cells. These cells have structural and functional properties relevant to retinal pigmented epithelial cells, a target in the course of AMD.</p> <p>Methods</p> <p>ARPE-19 cells were treated with 0, 10 or 25 μM 27-OHC for 24 hours. Levels of Aβ peptide, mitochondrial and endoplasmic reticulum (ER) stress markers, Ca²⁺homeostasis, glutathione depletion, reactive oxygen species (ROS) generation, inflammation and cell death were assessed using ELISA, Western blot, immunocytochemistry, and specific assays.</p> <p>Results</p> <p>27-OHC dose-dependently increased Aβ peptide production, increased levels of ER stress specific markers caspase 12 and gadd153 (also called CHOP), reduced mitochondrial membrane potential, triggered Ca²⁺dyshomeostasis, increased levels of the nuclear factor κB (NFκB) and heme-oxygenase 1 (HO-1), two proteins activated by oxidative stress. Additionally, 27-OHC caused glutathione depletion, ROS generation, inflammation and apoptotic-mediated cell death.</p> <p>Conclusions</p> <p>The cholesterol metabolite 27-OHC is toxic to RPE cells. The deleterious effects of this oxysterol ranged from Aβ accumulation to oxidative cell damage. Our results suggest that high levels of 27-OHC may represent a common pathogenic factor for both AMD and AD.</p

Description of a Prospective 17DD Yellow Fever Vaccine Cohort in Recife, Brazil

From September 2005 to March 2007, 238 individuals being vaccinated for the first time with the yellow fever (YF) -17DD vaccine were enrolled in a cohort established in Recife, Brazil. A prospective study indicated that, after immunization, anti-YF immunoglobulin M (IgM) and anti-YF IgG were present in 70.6% (IgM) and 98.3% (IgG) of the vaccinated subjects. All vaccinees developed protective immunity, which was detected by the plaque reduction neutralization test (PRNT) with a geometric mean titer of 892. Of the 238 individuals, 86.6% had IgG antibodies to dengue virus; however, the presence of anti-dengue IgG did not interfere significantly with the development of anti-YF neutralizing antibodies. In a separate retrospective study of individuals immunized with the 17DD vaccine, the PRNT values at 5 and 10 years post-vaccination remained positive but showed a significant decrease in neutralization titer (25% with PRNT titers < 100 after 5 years and 35% after 10 years)